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查锡良, Zhen Xu‡§†, Tomohiko Fukuda‡§, You Li‡, Xiliang Zha¶, Jun Qin , and Chuanyue Wu‡**
Vol. 280, No. 30, Issue of July 29, pp. 27631-27637, 2005,-0001,():
-1年11月30日
How cells couple and uncouple regulation of cellular processes such as shape change and survival is an important question in molecular cell biology. PINCH-1, a widely expressed protein consisting of five LIM domains and a C-terminal tail, is an essential focal adhesion protein with multiple functions including regulation of the integrin-linked kinase (ILK) level, cell shape, and survival signaling. We show here that the LIM1-mediated interaction with ILK regulates all these three processes. By contrast, the LIM4-mediated interaction with Nck-2, which regulates cell morphology and migration, is not required for the control of the ILK level and survival. Remarkably, a short 15-residue tail C-terminal to LIM5 is required for both cell shape modulation and survival, albeit it is not required for the control of the ILK level. The C-terminal tail not only regulates PINCH-1 localization to focal adhesions but also functions after it localizes there. These findings suggest that PINCH-1 functions as a molecular platform for coupling and uncoupling diverse cellular processes via overlapping but yet distinct domain interactions.
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查锡良, Xiu-Mei Cai, Bei-Bei Tao, Li-Ying Wang, , Yu-Long Liang, Jia-Wei Jin, Yong Yang, Ya-Li Hu and Xi-Liang Zha, *
Int. J. Cancer: 117, 905-912 (2005),-0001,():
-1年11月30日
PTEN is a major tumor suppressor gene that has been shown to inhibit cell invasion. Its mutation has been found in 20-40% of malignant gliomas. Meanwhile, the type III EGFR mutation (EGFRvIII), which was frequently found in gliomas, promoted cell invasion. In the present study, the effects of PTEN on cell invasion were investigated in U87DEGFR glioblastoma cells with EGFRvIII expression but missing PTEN. The cell invasion was downregulated by transfection of phosphatase-active forms of PTEN (wild-type and G129E) but not by PTEN (C124A) with an inactive phosphatase domain; the effects were correlated with decreased tyrosine phosphatase levels of FAK at Tyr397, which was increased by EGFRvIII. Overexpression of FAK mutant (Y397F) could partially mimic the effect of PTEN on cell invasion. Although EGFRvIII increased the levels of P-Akt and PTEN eliminated it, PI-3K inhibitors, wortmannin or Ly294002, could not decrease the cell invasion. In conclusion, PTEN could inhibit cell invasion even in the presence of the constitutively active EGFR; this inhibition depended on its protein phosphatase activity, partially by dephosphorylating FAK, but not depended on its lipid phosphatase activity.
EGFRvIII, PTEN, FAK, invasion
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查锡良, Yu-Long Lianga, Yi Fua, Si-Gang Chena, Xiu-Mei Caia, Jian-Min Sua, Jia-Wei Jina, Dong-Zhu Maa, Zeng-Xia Lia, Wen Zhanga, Xiliang Zhaa, b, *
FEBS Letters 558(2004)107-113,-0001,():
-1年11月30日
Evidence has been emerging to suggest that integrin could induce growth inhibition in some cell types. Some of the molecular mechanisms underlying growth arrest have been elucidated. We reported here that overexpression of integrin L1 imposed a growth inhibitory e
Integrin, p21CIP1, Hepatocellular carcinoma cell line, Trans, c, r, i, p, t, ional regulation, Promoter activity
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查锡良, Lineng Zhang, , Qiang Yu, Jianyu He and Xiliang Zha
Molecular and Cellular Biochemistry 262: 25-33, 2004.,-0001,():
-1年11月30日
N expression at both mRNA and protein levels compared with immortalized L02 hepatic cells. PTEN mRNA in SMMC-7721 hepatoma cells could be reduced by TGF-βI treatment. We also found that the phosphorylation levels of FAK in both of the hepatoma cell lines were higher than that in L02 hepatic cells. Transient expression of the PTEN gene in SMMC-7721 and HepG2 hepatoma cells resulted in decreased FAK phosphorylation. The level of FAK tyrosine phosphorylation appeared to be inversely correlated with the level of the PTEN protein. In summary, our results indicated that the function of the PTEN gene in hepatocarcinomas may be impaired mainly through point mutations and expression deficiency and that the defect of PTEN in tumor cells could alter the phosphorylation of FAK. (Mol Cell Biochem 262: 25–33, 2004)
PTEN,, mutation,, expression,, FAK,, hepatocellular carcinoma
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查锡良, Yi Fang, Liying Wang, Jiawei Jin and Xiliang Zha
Eur. J. Biochem. 268, 4513-4519 (2001),-0001,():
-1年11月30日
Most cell lines are resistant to tumor necrosis factor-a (TNF-a) cytotoxicity and require cotreatment of TNF-a with cycloheximide (Chx) to undergo apoptosis. Recently, the serine/threonine protein kinase, protein kinase B has been demonstrated to protect cells from apoptosis induced by TNF-a. In this study, we have shown that the human hepatocellular carcinoma cell line, SMMC-7721, was insensitive to TNF-a cytotoxicity and underwent apoptosis quickly in the presence of TNF-a and Chx. PKB levels decreased during TNF-a/Chx-induced apoptosis. No significant change in PKB levels was found in the presence of TNF-a or Chx alone. It seemed that the level of PKB closely correlated with apoptosis. The protein level of focal adhesion kinase (FAK) was reduced by 66% by transfecting FAK antisense cDNA recombinant vector into SMMC-7721 cells. We determined the apoptosis-induced effect of TNF-a/Chx on the FAK antisense cDNA transfectant cells. The results indicated that the percentage of apoptotic cells was enhanced at lower doses of TNF-a (10, 20 or 50U: mL21) and decreased at a higher dose of TNF-a (1000 U: mL21) in the transfected cells as compared to the control. Correspondingly, in the FAK antisense cDNA transfectant cells treated with lower doses of TNF-a in presence of 10 mg: mL21 Chx, the PKB level was lower, but in the FAK antisense cDNA transfectants treated with higher doses of TNF-a in presence of 10 mg:mL21 Chx, the PKB level was higher. In response to TNF-a alone, FAK antisense cDNA transfectants showed a decrease in the level of PKB. However, in the case of TNF-a cotreated with wortmannin, a specific inhibitor of phosphatidylinositol 3-kinase (PtdIns3K), the FAK antisense cDNA transfectants produced significantly less amounts of PKB than the control. It seemed that FAK could stimulate PKB levels through a pathway not involving PtdIns3K. These results suggest that FAK can affect the sensitivity of SMMC-7721 cells to TNF-a/Chx-induced apoptosis in a biphasic manner by regulating PKB levels.
focal adhesion kinase, protein kinase B, SMMC-7721 cells, tumor necrosis factor-a, cycloheximide, apoptosis.,
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